Fungal colonization in Cystic Fibrosis (CF): Epidemiology and antifungal resistance in a French cohort of CF patients – Focused on Aspergillus fumigatus colonization

Introduction: Cystic fibrosis (CF) is the major genetic inherited disease in the European Caucasian population, with an average of 1 in 3000 living births in France. Prognostic depend essentially on the lung impairments. While considerable attention therefore has been paid over recent decades to prevent and treat bacterial respiratory infections, we observed emergence of fungi colonization in CF respiratory tract. In particular, Aspergillus fumigatus represents the most common causative agent colonizing the airways of CF patients; it can be responsible for Allergic Bronchopulmonary Aspergillosis (ABPA). Since oral corticosteroids and itraconazole represent the mainstay of ABPA treatment, long-term therapy may increase the risk of acquired resistance to azoles that is mainly associated with amino acid substitutions in the CYP51A gene of A. fumigatus. Objective: First, we managed to have exhaustive epidemiological data on species of filamentous fungi able to colonize the airway tract of 300 CF patients followed-up in our national prospective study ("MucoFong" study – PHRC1902). Second, CF patients being chronically exposed to azole (especially to itraconazole), our study aimed to evaluate the prevalence of azole resistance in isolates prospectively collected from CF patients followed-up in seven French hospitals involved in our national prospective study. Third, we focused on the most prevalent species: Aspergillus fumigatus, studying the azole resistance at molecular level. To our knowledge, it is the first multicenter study focused on azole resistance of A. fumigatus in CF. Methods: A total of 243 sputa were analyzed using the same protocol in each centre. The MICs of antifungal drugs were evaluated for each isolate using the E-test ® strips. Focusing on A. fumigatus, a total of 87 isolates was collected in 85 patients. These isolates were characterized at the molecular level by targeting ITS, ß-tubulin and MAT-A/α genes. The CYP51A gene as well as its promoter was sequenced; a 3D Cyp51A protein homology model was built. Results and discussion: 300 patients were enrolled in this study. At inclusion time, most of them were adults colonized with A. fumigatus (about 35% of the patients). Scedosporium was isolated in 5%, and Exophiala in about 2%. Regarding antifungal susceptibility, isolates of Scedosporium and Exophiala exhibited antifungal resistance comparable with published data. Regarding A. fumigatus, a majority of isolates (88.1%) were found sensitive to itraconazole (MIC≤ 2μg/ml), and 2 new mutations were identified and localized within 3-dimensional Cyp51A protein model. To obtain insight into azole resistance of A. fumigatus, the results are analyzed taking into account clinical data, itraconazole exposition, and the potential correlation between the identified CYP5IA mutations and azole resistance is discussed based on the Cyp51A protein homology model

Evaluation and mangement of fungal risk in cystic fibrosis: first results of a national French study

Date du colloque&nbsp;: 06/2009</p

Phase shift between gas velocity and pressure in an orifice pulse tube

In order to investigate how the phase shift between pressure $P (t)$ and velocity of gas $V (t)$ affects the net refrigeration power of an orifice pulse tube, we have recorded at the cold end of the regenerator, when the temperature is constant at 173 K and 259 K, the net refrigeration power and the two signals of dynamic pressure and velocity of gas. The phase shift is computed from FFT of the two signals. If we maintain the amplitude of pressure $\Delta P = (P_{\max} -P_{\min})$ constant, the net refrigeration power varies as a function of the phase shift between pressure and velocity of gas

Outcomes of and predictors for colectomy in patients with Clostridium difficile associated diarrhoea

1 página de resumen, 1 póster. 21st European Congress of Clinical Microbiology and Infectious Diseases and 27th International Congress of Chemotherapy. 21st ECCMID/ 27th ICC. Milan, Italy, 7-10 may 2011.Infectious diseases are still major causes of death in developing countries especially Africa. Current chemotherapy rely almost exclusively on the use of antibiotics, however this is becoming ineffective due to global problem of antibiotic resistance. Hence the need for alternative chemotherapy through the use of viable Lactic Acid Bacteria (LAB) as probiotics. This study was carried out to characterize the probiotic potential of selected LAB strains isolated in Nigeria from traditional fermented dairy foods and cow's intestines samples in order to select strains for probiotic use in the gastrointestinal and urogenital tracts that will lessen possible infections in the tracts.Peer reviewe